Síntese totais convergentes de alcalóides aporfinoides empregando química de benzino

• Ano de defesa: 2014
• Autor(a) principal: Rossini, Allan Felipe da Costa [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Benzyne chemistry; [4+2] cycloaddition reaction; [1,3] sigmatropic rearrangement of hydrogen; Aporphine alkaloids; (±)-1,2,11-trimethoxynoraporphine; (±)-Omethylisothebaine; (±)-zanthoxyphylline iodide; Química de benzino; Reação de cicloadição [4+2]; Rearranjo sigmatrópico [1,3] de hidrogênio; Alcaloides aporfinoides; (±)-1,2,11-trimetoxinoraporfina; (±)-Ometilisotebaína; Iodeto de (±)-zantoxifilina
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=1361618; http://repositorio.unifesp.br/handle/11600/46311

The chemistry of benzyne has been successfully employed in several approaches involving the total synthesis of natural products and bioactive substances. Thus, due to the considerable importance of 2-(trimethylsilyl)aryl triflates in the current context of the chemistry of benzyne and due to the pronounced biological activities presented by aporphine alkaloids, including the potential of such compounds as agonists of dopamine receptors, antileishmanial activity and anticancer activity. We decided to accomplish the convergent total syntheses of the aporphine alkaloids (±)-1,2,11-trimethoxynoraporphine, (±)-O-methylisothebaine and (±)-zanthoxyphylline iodide, employing strategy that presents a sequence of pericyclic reactions, namely, [4+2] cycloaddition reaction followed by [1,3] sigmatropic rearrangement of hydrogen, which lead to the formation of the aporphine skeleton in a highly regioselective and diastereoselective manner. In this sense, we submitted 1-methylene-1,2,3,4-tetrahydroisoquinoline to the reaction with benzyne derivative formed from its corresponding 2-(trimethylsilyl)aryl triflate, under relatively mild reaction conditions, using CsF as base. Afterwards, the resulting key intermediate, which contains aporphine skeleton, was subjected to transformations of functional groups resulting in the aporphine alkaloids (±)-1,2,11-trimethoxynoraporphine, (±)-O-methylisothebaine and (±)-zanthoxyphylline iodide, which were obtained in 9, 10 and 10 rational steps, in overall yields of 38%, 27% and 31%, respectively.